Noradrenergic Deficits in Parkinson Disease Imaged with 11C-MeNER
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Noradrenergic Deficits in Parkinson Disease Imaged with 11C-MeNER. / Nahimi, Adjmal; Sommerauer, Michael; Kinnerup, Martin B; Østergaard, Karen; Winterdahl, Michael; Jacobsen, Jan; Schacht, Anna; Johnsen, Birger; Damholdt, Malene F.; Borghammer, Per; Gjedde, Albert.
In: Journal of Nuclear Medicine, Vol. 59, No. 4, 2018, p. 659-664.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Noradrenergic Deficits in Parkinson Disease Imaged with 11C-MeNER
AU - Nahimi, Adjmal
AU - Sommerauer, Michael
AU - Kinnerup, Martin B
AU - Østergaard, Karen
AU - Winterdahl, Michael
AU - Jacobsen, Jan
AU - Schacht, Anna
AU - Johnsen, Birger
AU - Damholdt, Malene F.
AU - Borghammer, Per
AU - Gjedde, Albert
N1 - © 2018 by the Society of Nuclear Medicine and Molecular Imaging.
PY - 2018
Y1 - 2018
N2 - Degeneration of noradrenergic neurons may underlie the disabling nonmotor symptoms in patients with Parkinson disease (PD). Quantification of the loss of noradrenergic neurons by means of neuroimaging has been limited by the lack of radioligands that are selective for noradrenergic neurotransmission. The radioligand (S,S)-11C-2-(α-(2-methoxyphenoxy)benzyl)morpholine (11C-MeNER) is a highly selective inhibitor of noradrenaline transporters, and PET studies suggest that this radioligand is suitable for quantitative neuroimaging of noradrenergic deficits in human brain in vivo. In the present investigation, we used PET with 11C-MeNER to map the density of noradrenaline transporters in groups of patients with PD and age-matched healthy controls. Methods: After administration of 11C-MeNER, 15 nondemented patients with PD and 10 healthy subjects underwent 90-min dynamic PET. We determined 11C-MeNER binding potential relative to nondisplaceable binding potential (BPND) by multilinear analysis, simplified reference tissue model 2, and multilinear reference tissue model 2. Results: Metabolism of 11C-MeNER did not differ between groups. The simplified reference tissue model 2 and the multilinear reference tissue model 2 were used to determine 11C-MeNER BPND11C-MeNER BPND was reduced in the PD group compared with the control subjects, with regionally significant declines in the thalamus and nucleus ruber. Tremor was associated with higher tracer binding in the PD group on multivariate regression analysis. Conclusion: To our knowledge, this was the first specific quantification of noradrenergic denervation in PD patients in vivo. In agreement with predictions from determinations in vitro, we discovered a decline of noradrenergic projections in vivo in brain of PD patients.
AB - Degeneration of noradrenergic neurons may underlie the disabling nonmotor symptoms in patients with Parkinson disease (PD). Quantification of the loss of noradrenergic neurons by means of neuroimaging has been limited by the lack of radioligands that are selective for noradrenergic neurotransmission. The radioligand (S,S)-11C-2-(α-(2-methoxyphenoxy)benzyl)morpholine (11C-MeNER) is a highly selective inhibitor of noradrenaline transporters, and PET studies suggest that this radioligand is suitable for quantitative neuroimaging of noradrenergic deficits in human brain in vivo. In the present investigation, we used PET with 11C-MeNER to map the density of noradrenaline transporters in groups of patients with PD and age-matched healthy controls. Methods: After administration of 11C-MeNER, 15 nondemented patients with PD and 10 healthy subjects underwent 90-min dynamic PET. We determined 11C-MeNER binding potential relative to nondisplaceable binding potential (BPND) by multilinear analysis, simplified reference tissue model 2, and multilinear reference tissue model 2. Results: Metabolism of 11C-MeNER did not differ between groups. The simplified reference tissue model 2 and the multilinear reference tissue model 2 were used to determine 11C-MeNER BPND11C-MeNER BPND was reduced in the PD group compared with the control subjects, with regionally significant declines in the thalamus and nucleus ruber. Tremor was associated with higher tracer binding in the PD group on multivariate regression analysis. Conclusion: To our knowledge, this was the first specific quantification of noradrenergic denervation in PD patients in vivo. In agreement with predictions from determinations in vitro, we discovered a decline of noradrenergic projections in vivo in brain of PD patients.
U2 - 10.2967/jnumed.117.190975
DO - 10.2967/jnumed.117.190975
M3 - Journal article
C2 - 28848039
VL - 59
SP - 659
EP - 664
JO - The Journal of Nuclear Medicine
JF - The Journal of Nuclear Medicine
SN - 0161-5505
IS - 4
ER -
ID: 202512185